Mesolimbic dopamine system

Acnte Drag Action/Drng Reinforcement and the Mesolimbic Dopamine System... 

Nicotine is the main psychoactive ingredient of tobacco and is responsible for the stimulant effects and abuse/ addiction that may result form tobacco use. Cigarette smoking rapidly (in about 3 sec ) delivers pulses of nicotine into the bloodstream. Its initial effects are caused by its activation of nicotinic acetylcholine (nACh) receptors. nACh receptors are ligand-gated ion-channels and pre- and postsynaptically located. Reinforcement depends on an intact mesolimbic dopamine system (VTA). nACh receptors on VTA dopamine neurons are normally activated by cholinergic innervation from the laterodorsal tegmental nucleus or the pedunculopontine nucleus. 

D Mello, G.D. Comparison of some behavioral effects of and electrical brain stimulation of the mesolimbic dopamine system in rats. Psychopharmacology (Berlin) 75 184-192, 1981. 

Both amphetamine and cocaine have also been reported to support intracranial self-administration in the mesolimbic/mesocortical dopaminergic system. Rats will self-administer cocaine into the medial prefrontal cortex (Goeders and Smith 1983). while amphetamine is self-administered into the orbitofrontal cortex of rhesus monkeys (Phillips and Rolls 1981) and the nucleus accumbens of rats (Hoebel et al. 1983 Monaco et al. 1981). These data indicate that the mesolimbic/mesocortical dopaminergic system is involved in the initiation of stimulant reinforcement processes, and this work suggests that the region of the nucleus accumbens, more specifically the mesolimbic dopamine system, may be an important substrate for reinforcing properties of several psychomotor stimulant drugs. 

Investigation of the neurochemical substrates for the psychostimulant effects of MDMA suggests a role for the mesolimbic dopamine system. Destruction of dopamine terminal fields in the nucleus accumbens significantly attenuated the locomotor activation produced by MDMA. A similar blockade of amphetamine-induced locomotor hyperactivity is known and was observed following amphetamine injection in these same rats. Such results support the hypothesis that at least one component of MDMA-induced hyperactivity is dopamine mediated and suggest that mesolimbic dopamine specifically is the critical substrate. In this way, MDMA resembles other classical psychostimulants like amphetamine and cocaine. Interestingly, evidence for functional cross-sensitization was suggested in the study in which an injection of amphetamine followed MDMA injection. 

Gold, L.H. Hubner, C.B. and Koob, G.F. A role for the mesolimbic dopamine system in the psychostimulant actions of MDMA. Psychopharmacology, in press. 

Joyce, E.M., and Koob, G.F. Amphetamine-, seopolamine-, and eaffeine-induced locomotor activity following 6-hydroxydopamine lesions of the mesolimbic dopamine system. Psychopharmacology 73 311-313, 1981. 

COMMENT I would dispute it within the dopamine system itself And I would dispute it about Parkinson s disease. I think that if you did a proper neuropsychological exam that you would pick up even smaller depletion effects. I think if you are looking for an overt complete terminal Parkinson situation, yes, you need a 99 percent depletion. But part of the problem is that the Parkinson situation involves not only the nigrostriatal system but also the mesolimbic dopamine system. There are plenty of studies in rats, and it is very easy to produce a Parkinsonian rat with a very discrete... 

French, E. Vantini, G. Contrera s, P. Pi 11 a pi 1, C. and Quirion, R. Phencyclidine (PCP) binding in the nucleus accumbens and PCP-induced hyperactivity are decreased following 60HDA lesions of the mesolimbic dopamine system. Neurosci Abst 10 1205, 1984. 

Additional studies in rats in vivo and in rat tissues or cells in vitro have focused on potential relationships between the effects of lead on neurotransmitter systems and neurobehavioral function. Lead exposure decreased dopamine binding sites, suggesting excess dopamine availability. The decreased dopamine binding was localized in the nucleus accumbens (mesolimbic dopamine system) but not the dorsal... 

Spyraki, C., Fibiger, H.C., and Phillips, A.G., Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system, Psychopharmacology, 79, 278, 1983. 

Corrigall, W.A., Coen, K.M., Adamson, K.L. Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res. 653 278, 1994. 

Berhow, M.T., Hiroi, N., Nestler, EJ. Regulation of ERK (extracellular signal regulated kinase), part of the neurotrophin signal transduction cascade, in the rat mesolimbic dopamine system by chronic exposure to morphine or cocaine. J. Neurosci. 16 4707, 1996. 

Opiates are clearly addictive, creating strong needs and cravings in the individual, as a result of the interaction with the mesolimbic dopamine system. Such dependence can lead to lifelong opiate use. This situation can be complicated by the fact that opiates are relatively non-toxic to body organs, so addicts can continue using them without... 

Shippenberg, T. S., Bals-Kubik, R., and Herz, A., Examination of the neurochemical substrates mediating the motivational effects of opioids Role of the mesolimbic dopamine system and D-l vs. D-2 dopamine receptors, J. Pharmacol. Exp. Ther., 265, 53, 1993. 

Overall, p agonists increase transmission in the mesolimbic dopamine system (Devine et al. 1993 Johnson and North 1992). They inhibit GABAergic neurons in the ventral tegmental area, disinhibiting dopamine activity. In contrast, k agonists inhibit dopamine release in the same system. As with other drugs of abuse, an influence on the mesolimbic dopamine is believed to mediate the positive reinforcing effects of opioids. 

Emotional effects Morphine creates a pleasant, euphoric state, which is an aspect of the behaviorally reinforcing effect. The subjective state produced by opioids is often described as ecstatic and is compared to a sexual experience. These effects are most likely mediated by iJ and possibly 5 receptors, and interactions with the mesolimbic dopamine system (Shippenberg et al. 1993 Di Chiara and North 1992 Wise 1989). In contrast, x opioids have dysphoric and psychotomimetic effects (Kumor et al. 1986). 

Beitner-Johnson D., Guitart X., and Nestler E.J. (1992) Neurofilament proteins and the mesolimbic dopamine system common regulation by chronic morphine and chronic cocaine in the rat ventral tegmental area./ Neurosci 12(6) 2165-2176. 

Willner, P. (1997) The mesolimbic dopamine system as a target for rapid antidepressant action. Int Clin Psychopharmacol 12 Suppl 3 S7-S14. 

Imperato A, Cabib S, Pughsi-Allegra S Repeated stressful experiences differently affect the time-dependent responses of the mesolimbic dopamine system to the stressor. Brain Res 601 333-336, 1993... 

Willner P, Scheel-Kruger J (eds) The Mesolimbic Dopamine System From Motivation to Action. New York, Wiley, 1991... 

To understand the long-term changes induced by drugs of abuse, their initial molecular and cellular targets must be identified. A combination of approaches in animals and humans, including functional imaging, has revealed the mesolimbic dopamine system as the prime target of addictive... 

As a general rule, all addictive drugs activate the mesolimbic dopamine system. The behavioral significance of this increase of dopamine is still debated. An appealing hypothesis is that mesolimbic dopamine codes for the difference between expected and actual reward and thus constitutes a strong learning signal (see The Dopamine Hypothesis of Addiction). 

The classification of NMDA antagonists as nonaddictive drugs was based on early assessments, which, in the case of PCP, have recently been questioned. In fact, animal research shows that PCP can increase mesolimbic dopamine concentrations and has some reinforcing properties in rodents. Concurrent effects on both thalamocortical and mesolimbic systems also exist for other addictive drugs. Psychosis-like symptoms can be observed with cannabinoids, amphetamines, and cocaine, which may reflect their effects on thalamocortical structures. For example, cannabinoids, in addition to their documented effects on the mesolimbic dopamine system, also enhance excitation in cortical circuits through presynaptic inhibition of GABA release. 

Cruz HG et al Bi-directional effects of GABA(B) receptor agonists on the mesolimbic dopamine system. Nat Neurosci 2004 7 153. [PMID 14745451]... 

Beitner-Johnson, Dana, and Eric J. Nestler. 1993. "Chronic Morphine Impairs Axoplasmic Transport in the Rat Mesolimbic Dopamine System." Neuroreport 5 57-60. 

Guitart, Xavier, Dana Bcitner-Johnson, David W. Marby, Therese A. Kosten, and Eric J. Nestler. 1992. "Fischer and Lewis Rat Strains Differ in Basal Levels of Neurofilament Proteins and Their Regulation by Chronic Morphine in the Mesolimbic Dopamine System." Synapse 12 242-53. 

Spyraki, Christina, Hans C. Fibiger, and Anthony G. Phillips. 1983. "Attenuation of Heroin Reward in Rats by Disruption of the Mesolimbic Dopamine System." Psychopharmacology 79 278-83. 

Trulson, Michael E., John C. Joe, Susan Babb, and Joachim D. Raese. 1987. "Chronic Cocaine Administration Depletes Tyrosine Hydroxylase Immuno reactivity in the Mesolimbic Dopamine System in the Rat Brain Quantitative Light Microscopic Studies." Brain Research Bulletin 19 39-45. 

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